Damrongsak Faroongsarng

The Swelling & Water Uptake of Tablets III: Moisture Sorption Behavior of Tablet Disintegrants

AbstractWater vapor sorption properties and the thermal behavior of four disintegrants including microcrystalline cellulose (Avicel PH102), croscarmellose sodium (Ac-di-sol), corn starch, and sodium starch glycolate (Primojel), were studied. They all exhibited type II-like isotherm. The apparent monolayer sorption for each of disintegrants was found to be significantly greater than the specific surface obtained from nitrogen adsorption. It is proposed that water molecules interact with specific sites on the disintegrant glassy polymer. Water tends to stay as a condensed phase on the polymer, rather than to diffuse into the bulk. Water plasticization caused glass transition temperature (Tg) of all disintegrant polymers to decrease. It facilitated a change from glass to the rubber state. Because the sorption sites were in the glassy state, the change from glass to rubber, which in turn kinetically reduced the available sites, would reflect the sorption capacity of a disintegrant polymer. In addition, the di...

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

AbstractSpray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibite...

Compression behavior of spray dried rice starch

Compression behaviors of spray dried rice starch (SDRS), as well as pregelatinized starch (PS), and microcrystalline cellulose (MCC) were characterized using Heckel analysis. SDRS was found to undergo plastic deformation with lower elasticity compared with PS. SDRS showed very low fragmentation tendency due to the fact that the difference between extrapolated and actual densification of its Heckel plot was low. Having aggregate sphere in shape, its densification could be initiated by deaggregation and tight packing without requiring high pressure. The above evidence explains why the compactibility of SDRS is excellent. MCC on the other hand, showed some fragmentation before undergoing plastic deformation. The fragmentation might have increased the contacts among particles which resulted in higher crushing strength of the tablets compared with that of SDRS. The slope of the Heckel plot of a mixture of each excipient and hydrochlorothiazide fairly agreed with the summation of the weight fraction of each component. The deformation of the mixture tested could be easily predicted. Since SDRS possesses both good compactibility and flowability, this new direct compression excipient has a high potential for successful tablet formulation.

Thermal porosity analysis of croscarmellose sodium and sodium starch glycolate by differential scanning calorimetry

The aim of the study was to demonstrate the applicability of differential scanning calorimetry (DSC) on porosity analysis for cellulose and starch. Croscarmellose sodium (CCS) and sodium starch glycolate (SSG) were allowed to sorb moisture in 85%, 90%, 95%, and 100% relative humidity (RH) at 40°C for 24 hours. The pretreated samples were then subjected to DSC running temperature ranging from 25°C to −50°C at a cooling rate of 10°C/min. The cooling traces of water crystallization, if present, were transformed to porosity distribution via capillary condensation using Kelvins equation. The porosity analysis of CCS and SSG was also done using nitrogen adsorption as a reference method. It was found that sorbed water could not be frozen (in cases of 85% and 90% RH) until the moisture content exceeded a cutoff value (in cases of 95% and 100% RH). The nonfreezable moisture content was referred to tightly bound, plasticizing water, whereas the frozen one may be attributed to loosely bound water condensation in pore structure of CCS and SSG surfaces. Not only capillary condensation but also the tightly bound, nonfreezable monolayer water lying along the inner pores of the surface contributed to porosity determination. Good agreement with less than 5% deviation of mean pore size was observed when the results were compared with nitrogen adsorption. The narrower pore size distributions, however, were obtained because of the limitations of the technique. It was concluded that pore analysis by DSC could be successful. Further research needs to be done to account for limitations and to extend the applicability of the technique.

The Swelling of Core Tablets During Aqueous Coating I: A Simple Model Describing Extent of Swelling and Water Penetration for Insoluble Tablets Containing a Superdisintegrant

AbstractA simple mathematical model was established to describe changes of tablet thickness due to swelling and water penetration during aqueous coating process. The model was illustrated by a simple linear equation, i.e.; D = -(α/(l+e))l1,+(α/(l+e))l0; where D, l0,11, α and e are the depth of water penetrating into tablets, initial tablet thickness, the remaining dried core tablet thickness, swelling and porosity parameters, respectively. The data from dicalcium phosphate dihydrate(Ditab) tablets containing a super-disintegrant may be fitted into the model showing significant statistical correlation. The model was valid for describing the extent of tablet swelling and water penetration during aqueous coating.

The Role of Liquid Water Uptake by an Insoluble Tablet Containing a Disintegrant

AbstractThe hydration capacity of each of four disintegrants including microcrystalline cellulose (Avicel PH102), corn starch, croscarmellose sodium (Ac-di-sol) and sodium starch glycolate (Primojel) was determined to express the hydrophilicity. The complete pore structure, and the water uptake of unmilled dicalcium phosphate dihydrate (Di-Tab) tablets containing one of above disintegrants at 15% w/w level were studied It was found that the majority of the tablet porosity was made up by macropores which were accessed by mercury intrusion There was no statistically significant difference among pore volume-size distributions of table samples The water uptake results were treated by the empirical form of Washburn liquid penetration equation with appropriate experimental setup. It was possible to determine the significance of the empirical parameters drawn from the equation It was found that the hydrophilic nature of excipients present in a tablet played a major role in water uptake phenomenon It was suggeste...

Ambroxol lozenge bioavailability : an open-label, two-way crossover study of the comparative bioavailability of ambroxol lozenges and commercial tablets in healthy thai volunteers.

ObjectiveTo compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet.DesignOpen-label, two-way crossover study.MethodEach formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After administration, serial blood samples were collected over a 24-hour period and the plasma concentration of ambroxol was subsequently measured using high performance liquid chromatography with ultraviolet detection after liquid-liquid extraction. Pharmacokinetic parameters were analysed by a noncompartmental pharmacokinetic model and compared between formulations using analysis of variance with a significance level of 0.05.ResultsThe point estimates (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) ratios between lozenge and commercial tablet were 1.07 (0.89 to 1.28) and 1.20 (1.04 to 1.40), respectively. The point estimate (90% CI) of the difference between formulations for time to Cmax was 0.40 (−0.20 to 1.00).ConclusionThe two formulations under test were not bioequivalent based on the stipulated bioequivalence criteria. The bioavailability from the ambroxol lozenge might be better, since the 90% CI of the AUC0-∞ fell outside the bioequivalence range, and its range was narrower. The difference in rate of absorption was not conclusive because ambroxol was delivered from the lozenge by two parallel processes, namely absorption via oral and gastrointestinal mucosa. The additional oral mucosal absorption might not only contribute more absorption but also introduce variability compared with that of tablet administration. The relative importance of oral versus gastrointestinal mucosal absorption of ambroxol from the lozenge formulation, and the clinical significance of this, requires further study.

Study on tablet binding and disintegrating properties of alternative starches prepared from taro and sweet potato tubers.

To demonstrate the potential alternative sources of starch used in tablet formulations, starches from taro (TS) and sweet potato (SPS) tubers were prepared with obtained yields of 11.0 and 9.6%, respectively. Both TS and SPS met USP22-NF17 identification and specifications. Their equilibrium moisture contents and gelatinization temperatures were comparable with those of commercial starch, whereas amylose contents of TS and SPS were 21.38% w/w and 41.76% w/w, respectively. Both were found to possess similar flow characteristics. To evaluate TS and SPS as granulating agents and disintegrants, tablets with controlled compression loads were prepared by incorporating a starch candidate with dibasic calcium phosphate in paste and powders forms, respectively. Tablets were then evaluated based on compressibility, friability, and disintegration. It was found that the binding and disintegrating performance of both TS and SPS was similar to that of commercial cornstarch.

Thermal behavior of a pharmaceutical solid acetaminophen doped withp-aminophenol

Thermal behavior of a series of acetaminophen (APAP) doped withp-aminophenol (PANP) was studied by differential scanning calorimetry (DSC) to determine whether it exhibited a eutectic system. Within the temperature range of 120 to 200° C, accurately weighed (1–2 mg) samples sealed in hermetic pans were calorimetrically scanned with a low scanning rate of 1° C/min. The mixture formed a single eutectic with the composition ratio APAP/PANP of 0.6/0.4 at a temperature of 138° C, where it liquefied. Melting began as early as at the eutectic point, which was below the melting temperature of APAP (169° C). The melting point as well as heat of APAP fusion was depressed with the increase in doped PANP. It was postulated that there might be a deficit heat of APAP fusion in APAP doped with PANP, which was coincident with the heat consumed by early liquefaction. The deficit heat was used to correct fraction molten in the van’t Hoff law of purity determination. It was found that the purity determination of APAP doped with PANP was comparable to the UV-spectroscopic method up to the maximum doped PANP level of 8 mol percent. It was concluded that DSC was able to approach early heat of liquefaction of APAP doped with PANP. The van’t Hoff law may be applicable to the determination of APAP with the presence of PANP as a eutectic impurity.

Theoretical Aspects of Differential Scanning Calorimetry as a Tool for the Studies of Equilibrium Thermodynamics in Pharmaceutical Solid Phase Transitions

Although differential scanning calorimetry (DSC) is a non-equilibrium technique, it has been used to gain energetic information that involves phase equilibria. DSC has been widely used to characterize the equilibrium melting parameters of small organic pharmaceutical compounds. An understanding of how DSC measures an equilibrium event could make for a better interpretation of the results. The aim of this mini-review was to provide a theoretical insight into the DSC measurement to obtain the equilibrium thermodynamics of a phase transition especially the melting process. It was demonstrated that the heat quantity obtained from the DSC thermogram (ΔH) was related to the thermodynamic enthalpy of the phase transition (ΔHP) via: ΔH = ΔHP/(1 + K− 1) where K was the equilibrium constant. In melting, the solid and liquefied phases presumably coexist resulting in a null Gibbs free energy that produces an infinitely larger K. Thus, ΔH could be interpreted as ΔHP. Issues of DSC investigations on melting behavior of crystalline solids including polymorphism, degradation impurity due to heating in situ, and eutectic melting were discussed. In addition, DSC has been a tool for determination of the impurity based on an ideal solution of the melt that is one of the official methods used to establish the reference standard.